2. Academic Validation
  3. NF-κB-Inducing Kinase Provokes Insulin Resistance in Skeletal Muscle of Obese Mice

NF-κB-Inducing Kinase Provokes Insulin Resistance in Skeletal Muscle of Obese Mice

  • Inflammation. 2023 May 12. doi: 10.1007/s10753-023-01820-7.
Xueqin Chen 1 2 3,  Zhuoqun Liu 3,  Wenjun Liu 3,  Shu Wang 4,  Ran Jiang 1 2,  Kua Hu 1 2,  Liang Sheng 5,  Guangxu Xu 6,  Xinhui Kou 7,  Yu Song 8 9
Affiliations

Affiliations

  • 1 Department of Pharmacology, Pharmacy College, Xinxiang Medical University, Xinxiang, Henan, 453003, China.
  • 2 Xinxiang key Laboratory for Epigenetic Molecular Pharmacology, Xinxiang, Henan, 453003, China.
  • 3 Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
  • 4 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210100, China.
  • 5 Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China. lgsheng@njmu.edu.cn.
  • 6 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210100, China. xuguangxu1@126.com.
  • 7 Department of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, China. xkou13@fudan.edu.cn.
  • 8 Department of Pharmacology, Pharmacy College, Xinxiang Medical University, Xinxiang, Henan, 453003, China. songyugzyx@163.com.
  • 9 Xinxiang key Laboratory for Epigenetic Molecular Pharmacology, Xinxiang, Henan, 453003, China. songyugzyx@163.com.
PMID: 37171694 DOI: 10.1007/s10753-023-01820-7
Abstract

Skeletal muscle is crucial for preserving glucose homeostasis. Insulin resistance and abnormalities in glucose metabolism result from a range of pathogenic factors attacking skeletal muscle in obese individuals. To relieve Insulin resistance and restore glucose homeostasis, blocking the cell signaling pathways induced by those pathogenic factors seems an attractive strategy. It has been discovered that Insulin sensitivity in obese people is inversely linked with the activity of NF-κB inducing kinase (NIK) in skeletal muscle. In order to evaluate NIK's pathological consequences, mechanism of action, and therapeutic values, an obese mouse model reproduced by feeding a high-fat diet was treated with a NIK inhibitor, B022. C2C12 myoblasts overexpressing NIK were utilized to assess Insulin signaling and glucose uptake. B022 thus prevented high-fat diet-induced NIK activation and Insulin desensitization in skeletal muscle. The Insulin signaling in C2C12 myoblasts was compromised by the upregulation of NIK brought on by oxidative stress, lipid deposition, inflammation, or adenoviral vector. This inhibition of Insulin action is mostly due to an inhibitory serine phosphorylation of IRS1 caused by ERK, JNK, and PKC that were activated by NIK. In summary, NIK integrates signals from several pathogenic factors to impair Insulin signaling by igniting a number of IRS1-inhibiting kinases, and it also has significant therapeutic potential for treating Insulin resistance.

Keywords

NF-κB-inducing kinase; insulin receptor substrate 1.; insulin resistance; skeletal muscle.

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